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Roles of phospholipase Cβ4 in synapse elimination and plasticity in developing and mature cerebellum

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Abstract

The β isoforms of phospholipase C (PLCβs) are thought to mediate signals from metabotropic glutamate receptor subtype 1 (mGluR1) that is crucial for the modulation of synaptic transmission and plasticity. Among four PLCβ isoforms, PLCβ4 is one of the two major isoforms expressed in cerebellar Purkinje cells. The authors have studied the roles of PLCβ4 by analyzing PLCβ4 knock-out mice, which are viable, but exhibit locomotor ataxia. Their cerebellar histology, parallel fiber synapse formation, and basic electrophysiology appear normal. However, developmental elimination of multiple climbing fiber innervation is clearly impaired in the rostral portion of the cerebellar vermis, where PLCβ4 mRNA is predominantly expressed in the wild-type mice. In the adult, long-term depression is deficient at parallel fiber to Purkinje cell synapses in the rostral cerebellum of the PLCβ4 knockout mice. The impairment of climbing fiber synapse elimination and the loss of long-term depression are similar to those seen in mice defective in mGluR1, Gαq, or protein kinase C. Thus, the authors’ results strongly suggest that PLCβ4 is part of a signaling pathway, including the mGluR1, Gαq and protein kinase C, which is crucial for both climbing fiber synapse elimination in the developing cerebellum and long-term depression induction in the mature cerebellum.

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Authors and Affiliations

  1. Department of Physiology, Kanazawa University School of Medicine, Takara-machi, 920-8640, Kanazawa, Japan

    Kouichi Hashimoto & Masanobu Kano

  2. Department of Physiology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku, 162-8666, Tokyo, Japan

    Mariko Miyata

  3. Department of Anatomy, Hokkaido University School of Medicine, 060-0807, Sapporo, Japan

    Masahiko Watanabe

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  1. Kouichi Hashimoto
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  2. Mariko Miyata
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  3. Masahiko Watanabe
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  4. Masanobu Kano
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Correspondence to Masanobu Kano.

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Hashimoto, K., Miyata, M., Watanabe, M. et al. Roles of phospholipase Cβ4 in synapse elimination and plasticity in developing and mature cerebellum. Mol Neurobiol 23, 69–82 (2001). https://doi.org/10.1385/MN:23:1:69

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